|
|
Roles of sulfonylurea receptor 1 and multidrug resistance protein 1 in modulating insulin secretion in human insulinoma |
Cheng-Jiang Li, Hua-Li Zhou, Jun Li, Hong-Tian Yao, Rong Su and Wen-Peng Li |
Hangzhou, China
Author Affiliations: Department of Endocrinology (Li CJ, Zhou HL and Li WP), Department of Pathology (Li J and Yao HT), and Key Laboratory of Multi-organ Transplantation of Ministry of Public Health (Su R), First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Corresponding Author: Hua-Li Zhou, MD, Department of Endocrinology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China (Tel: 86-571-87236866; Fax: 86-571-87236874; Email: lhlzhou@hotmail.com) |
|
|
Abstract BACKGROUND: Sulfonylurea receptor 1 (SUR1) and multidrug resistance protein 1 (MRP1) are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion.
METHODS: Fasting glucose, insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma patients. Insulin content, SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence.
RESULTS: Insulinoma patients presented the typical demons-trations of Whipple(s triad. Fasting glucose of each insulinoma patient was lower than 2.8 mmol/L, and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high glucose. Immunohistochemistry and immunofluorescence staining showed that SUR1 increased, but MRP1 decreased in insulinoma compared with the adjacent islets.
CONCLUSIONS: The hypersecretion of insulin in insulinomas might be, at least partially, due to the enrichment of SUR1. In contrast, MRP1, which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.
|
|
|
|
|
|
|
|